Visceral pain is a common and debilitating component of many human diseases. Painful sensations are elicited from hollow visceral organs by mechanical and chemical stimuli. The mechanisms for detecting nociceptive mechanical stimulation under normal and pathologic conditions remain largely unknown. The presence of mechanosensitive ion channels in peripheral sensory neurons suggests a possible role in and potential therapeutic targets for modulation of visceral pain. The purpose of this research proposal is to determine the relevance of the acid-sensing ion channel 3 subunit (ASIC3) in visceral nociception under normal and hyperalgesic states. The proposed study utilizes behavioral testing with colorectal distension (CRD) in inbred and transgenic mice, molecular analysis of primary afferent neurons with real-time polymerase-chain reaction (PCR) and immunohistochemistry, and electrophysiological recordings with an in vitro colon-pelvic nerve preparation to address this question.